Heterosexual transmission of HIV from both men to women and women to men is the principal mode by which the virus is spread, but the exact mechanisms of transmission are not clearly understood. This study is designed to determine the 50% Macaque Infectious Dose (MID50) for cell-free SIVMne delivered by the intravaginal route in adult Macaca nemestrina.. The intravaginal MID50 will be used as the basis for selecting virus challenge doses in candidate vaccine and antiviral drug trials. In addition to determining the MID50 for SIVMne, we simultaneously examined the kinetics of seroconversion in intravaginally infected animals by monitoring immunoglobulin levels and isotypes in several mucosal compartments and plasma and compared the antibody response with those responses observed in intravenously inoculated macaques. Two adult female M. nemestrina were inoculated intravaginally with 104 TCID of uncloned SIVMne in June 1996. Two females were inoculated intravenously wit h the same dose and virus. Both intravenously inoculated macaques became infected and developed a strong plasma antibody response to SIV. One of the intravaginally inoculated animals became infected and seroconverted while the other remained virus negative but showed a transient plasma antibody response. SIV-specific antibodies were detected in the tears, plasma, saliva, rectal washes, and vaginal washes of all 3 of the infected macaques. These 4 macaques were euthanized and histology was performed on the tissues at 52 weeks post-inoculation. Two additional macaques were inoculated intravaginally with 103 TCID in December 1997. Both of these macaques have seroconverted and have shown transient viremia. Both macaques had detectable viral-specific antibody in vaginal washes. These 2 macaques were euthanized and histololgy was performed on the tissues at 18 weeks post-inoculation. FUNDING NIH grant RR00166.